We have found some spontaneous fusion between host cells and tumor cells in the mouse Ehrlich ascites tumor (EAT), resulting in hybrids that can grow as malignant cells after elimination of some chromosomes. This was suspected from the karyotypic findings on EAT long maintained in the CF1 mice, and confirmed from the acquisition of host specific T6 chromosome markers by the tumor cells at various generations after a transfer of EAT from CF1 into the CBA/HT6 strain hosts. A transfer of EAT prelabeled with 3HTdr into unlabeled CBA/HT6 hosts helped further in identifying hybrid karyotypes. We shall compare the extent of the hybridization in the EAT maintained in a random bred strain, inbred strain and following an interstrain transfer, to examine whether the latter accelerates this process. We shall test whether, after an allogeneic transfer of EAT from the CBA/HT6 to the CF1 strain, donor- specific T6 chromosomes are lost from the hybrids. A prolonged passage of EAT from the CF1 into the CBA/HT6 strain was found to cause antigenic changes; it acquired tumorogenicity by the subcutaneous route in the CBA/HT6 strain, but lost its tumorogenicity by the same route in the CF1 strain. We shall examine with the aid of immunofluorescence techniques, whether such passage leads to an acquisition of host specific H-2 antigen. Two way subcutaneous transplants of EAT long maintained in the inbred parent (CBA/HT6) and F1 hybrid (C57B1 times CBA/HT6) will be used to evaluate whether such EAT behaves as donor-specific homografts. Host showing tumor regression by the subcutaneous route will be tested for an immunity to the EAT in the ascites form. The identity of the hybridizing host cells will be examined from morphological studies, and their nature and source explored by quantitating hybridization in the EAT transplanted in the irradiated hosts of chromosomally-marked marrow chimeras. Since hybridization followed by chromosome loss may explain universal transplantability of EAT across strain barriers, the presence of this phenomenom will be examined in other EAT lines and Krebs-2 ascites tumor.